Cluster headache

The etiology is not known. A history of head trauma, heavy cigarette smoking, and heavy alcohol intake are all associated with cluster headache, although no causal relationship has been found.[8] However, smoking cessation has no effect on the condition.[1][9] Some studies have reported an association between cluster headache and sleep apnea, with some patients having improved headache control with treatment of their sleep apnea.[10][11]

The condition does appear to be heritable, with first-degree relatives of affected people having an estimated 14-fold increased risk of developing the disorder.[1][5][12] Candidate gene and genome-wide association studies have identified some genes that may be involved.[13] However, in most cases there is no family history of cluster headache.

The pathogenesis is complex and not understood completely. The three cardinal features of the disorder are:

Trigeminal distribution of the pain
Ipsilateral cranial autonomic symptoms
Circadian/circannual pattern of attacks.

There is a well-described physiologic reflex arc, the trigeminal autonomic reflex, that is thought to potentiate the trigeminal pain and cranial autonomic features of cluster headache.[14][15][16] Nociceptive information from pain-sensitive structures in the face, and particularly the dura mater and cerebral blood vessels, is carried to the brainstem via the trigeminal nerve. Within the brainstem, these trigeminal fibers synapse in the area known as the trigeminocervical complex (TCC). Information is then sent to the hypothalamus, thalamus, and cortex via the pain-processing pathways. Afferent trigeminal signals arriving at the TCC activate the cranial parasympathetic system. This results in increased firing of the parasympathetic fibers innervating facial structures, and causes the autonomic features seen in an attack. Neuropeptides, including calcitonin gene-related peptide (CGRP), released at these parasympathetic nerve endings cause further irritation of the trigeminal sensory nerve endings, and this potentiates the reflex arc further. The timing of cluster attacks and the agitation associated with attacks have led to the belief that the hypothalamus must play a role in the pathophysiology of cluster headache. This theory has been supported by functional neuroimaging studies that have detected activation of the posterior hypothalamic region ipsilateral to the pain during a cluster attack.[14][15] Further studies have demonstrated functional interconnections between the pain matrix in the cortex, hypothalamus, and brainstem that can stimulate the trigeminovascular system and trigeminal autonomic reflexes during cluster bouts, suggesting a more top-down mechanism or central hypothesis for cluster attacks.[14][15]

International Classification of Headache Disorders-3 (ICHD-3)[2]

Trigeminal autonomic cephalalgias:

3.1 Cluster headache

3.1.1 Episodic cluster headache
3.1.2 Chronic cluster headache.

3.2 Paroxysmal hemicrania

3.2.1 Episodic paroxysmal hemicrania
3.2.2 Chronic paroxysmal hemicrania.

3.3 Short-lasting unilateral neuralgiform headache attacks

3.3.1 Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)
- 3.3.1.1 Episodic SUNCT
- 3.3.1.2 Chronic SUNCT
3.3.2 Short-lasting unilateral neuralgiform headache attacks with autonomic features (SUNA)
- 3.3.2.1 Episodic SUNA
- 3.3.2.2 Chronic SUNA

3.4 Hemicrania continua

3.5 Probable trigeminal autonomic cephalalgia

3.5.1 Probable cluster headache
3.5.2 Probable paroxysmal hemicrania
3.5.3 Probable SUNCT
3.5.4 Probable hemicrania continua.

Etiology

Pathophysiology

Classification